Friedreich Ataxia (FRDA) is an autosomal recessive disease in which a mitochondrial protein, frataxin, is severely decreased in its expression. In addition to progressive ataxia, patients with FRDA often develop a cardiomyopathy that can be hypertrophic. This cardiomyopathy is unlike the sarcomeric hypertrophic cardiomyopathies in that the hypertrophy is associated with massive mitochondrial proliferation within the cardiomyocyte rather than contractile protein overexpression. This is associated with atrial arrhythmias, apoptosis, and fibrosis over time, and patients often develop heart failure leading to premature death. The differences between this mitochondrial cardiomyopathy and the more common contractile protein hypertrophic cardiomyopathies can be a source of misunderstanding in the management of these patients. Although imaging studies have revealed much about the structure and function of the heart in this disease, we still lack an understanding of many important clinical and fundamental molecular events that determine outcome of the heart in FRDA. This review will describe the current basic and clinical understanding of the FRDA heart, and most importantly, identify major gaps in our knowledge that represent new directions and opportunities for research.
Keywords: CMR, cardiac magnetic resonance; FDA, U.S. Food and Drug Administration; FRDA, Friedreich ataxia; Friedreich ataxia; GAA, triplet expansion in first intron of the Friedreich ataxia gene; HF, heart failure; LV, left ventricle; LVEF, left ventricular ejection fraction; LVMI, left ventricular mass index; RV, right ventricle; cardiomyopathy; frataxin; heart; mitochondria.
© 2022 The Author.